Vertebrate cells depend on externally produced factors for growth, differentiation and survival. These factors can be in the form of diffusible, molecules that act at a distance from their site of synthesis. Alternatively these factors can be in the form of cell-surface-bound molecules that rely on cell-to-cell contact for their function. In many cases, different cell types may interact in a reciprocal manner in that both cell types produce factors that affect the other cell type. Vertebrates rely on these reciprocal interactions during embryogenesis and during the response to injury and disease.
Interdependence of cells and tissues plays important roles in the vertebrate nervous system. The nervous system is composed of neurons and neuroglial support cells. Peripheral nervous system axons are ensheathed by neuroglial cells (Schwann cells) and target organs which include skin, sensory receptors, muscle and other neurons. Additionally, peripheral axons interact with components of the central nervous system in the spinal cord. These include neurons and neuroglial cells such as astrocytes and oligodendrocytes .
It is well established that neurons and the tissues and cells with which they interact are dependent on each other for trophic support. This relationship is mediated by factors (proteins) produced by neurons that maintain the viability of target tissues (e.g. motor neuron derived factors that maintain muscle integrity) and neurotrophic factors produced by target (and other) tissues that maintain neuronal viability (e.g. muscle derived factors that maintain motor neuron viability). This interdependence plays an important role in embryonic development, maintenance of viability and response to injury in the nervous system and its targets.
The survival of various neuronal populations has been thought to be dependent only upon neurotrophic factors produced by targets of innervation. Recently it has been realized that neurotrophic factors are also derived from axonally associated cells (periaxonal glia), soma associated (perisomatic) cells (e.g. glia and efferent synapses) and from autocrine sources. These proteins are taken up by neurons where they exert their effect at the cell body . Neurotrophic factors either maintain the viability of the neuron or induce specific effects such as axonal extension, sprouting and other responses to injury and disease. Examples include factors such as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and related molecules as well as ciliary neurotrophic factor (CNTF), insulin like growth factor (IGF) and fibroblast growth factors (FGF's) that all have neurotrophic activity and are derived from neuronally associated tissues as diverse as muscle, Schwann cells and spinal cord astrocytes and other neurons (e.g., Nishi, Science (1994) 265:1052).
The identification of pharmaceutical products or agents which induce the endogenous production of trophic factors would be beneficial treatment of diseases which involve trophic support.